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Lateral mesoderm-derived mesenchymal stem cells with robust osteochondrogenic potential and hematopoiesis supporting ability

ABSTRACT: Lateral mesoderm-derived mesenchymal stem cells with robust osteochondrogenic potential and hematopoiesis supporting ability

PROVIDER: PRJNA755197 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15465955_1.fastq.gz	Fastqsanger.gz
	SRR15465955_2.fastq.gz	Fastqsanger.gz
	SRR15465956_1.fastq.gz	Fastqsanger.gz
	SRR15465956_2.fastq.gz	Fastqsanger.gz
	SRR15465957_1.fastq.gz	Fastqsanger.gz

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Lateral mesoderm-derived mesenchymal stem cells with robust osteochondrogenic potential and hematopoiesis supporting ability

Project description:Here, hiPSCs were induced to differentiate to mesenchymal stem cells (MSCs) through the intermediate stage of lateral mesoderm (LM). We sequenced mRNA samples of LM and LM-MSCs to generate the gene expression profiles of these cells.

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Lateral Mesoderm-Derived Mesenchymal Stem Cells With Robust Osteochondrogenic Potential and Hematopoiesis-Supporting Ability.

Project description:Mesenchymal stem cells (MSCs) are among the most promising cell sources for the treatment of various diseases. Nonetheless, the therapeutic efficacy in clinical trials has been inconsistent due to the heterogeneity of MSCs, which may be partially attributed to their undefined developmental origins. The lateral mesoderm is also a developmental source of MSCs that constitute appendicular skeletal elements in the developing vertebrate embryo. However, it is difficult to isolate homogeneous lateral mesoderm (LM)-derived MSCs from bone tissues or bone marrow due to the lack of understanding of their characteristics. Herein, we successfully established an efficient differentiation protocol for the derivation of MSCs with a LM origin from human pluripotent stem cells (hPSCs) under specific conditions. LM-MSCs resembled bone marrow-derived MSCs (BMSCs) with regard to cell surface markers, global gene profiles, and immunoregulatory activity and showed a homeodomain transcription factor (HOX) gene expression pattern typical of skeletal MSCs in long bones. Moreover, we demonstrated that LM-MSCs had an increased osteogenic/chondrogenic differentiation capacity and hematopoietic support potential compared to BMSCs. These homogeneous LM-MSCs may serve as a powerful tool for elucidating their precise role in bone formation and hematopoiesis and could be a potentially ideal cell source for therapeutic applications.

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Expression profiling of retinoic acid targets in lateral mesoderm from Xenopus laevis embryos

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Development of the chicken lateral plate mesoderm and forelimb mesenchyme

Project description:Development of the chicken lateral plate mesoderm and forelimb mesenchyme

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Development of the chicken lateral plate mesoderm and forelimb mesenchyme

Project description:The lateral plate mesoderm (LPM) is a transient tissue that produces a diverse range of differentiated structures, including the limbs. However, the molecular mechanisms that drive early LPM specification and development are poorly understood. In this study, we utilize single-cell transcriptomics to define the cell-fate decisions directing LPM specification, subdivision, and early initiation of the forelimb mesenchyme in chicken embryos. We establish a transcriptional atlas and global cell-cell signalling interactions in progenitor, transitional and mature cell types throughout the developing forelimb field.

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Expression profiling of retinoic acid targets in lateral mesoderm from Xenopus laevis embryos

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Chromatin remodeler Brahma safeguards labile canalization of cardiac mesoderm differentiation

Project description:Differentiation proceeds along a continuum of increasingly fate-restricted intermediates, referred to as canalization. Canalization is essential for stabilizing cell fate, but mechanisms underlying robust canalization are unclear. Here we show that the BRG1/BRM-associated factor (BAF) chromatin remodeling complex ATPase gene Brm safeguards cell identity during directed cardiogenesis of mouse embryonic stem cells. Despite establishment of well-differentiated precardiac mesoderm, Brm-null cells predominantly became neural precursors, violating germ layer assignment. Trajectory inference showed sudden acquisition of non-mesodermal identity in Brm-null cells, consistent with a new transition state referred to as a saddle-node bifurcation. Mechanistically, loss of Brm prevented de novo accessibility of cardiac enhancers while increasing expression of neurogenic factor POU3F1, preventing expression of neural suppressor REST, and disrupting composition of BRG1 complexes. Brm mutant identity switch was overcome by increasing BMP4 levels during mesoderm induction. Mathematical modeling supports all our observations. In the mouse embryo, Brm deletion exacerbated mesoderm-deleted Brg1 mutant phenotypes, severely compromising cardiogenesis, unmasking an in vivo role for Brm. Our results reveal Brm as a compensable safeguard of the fidelity of mesoderm chromatin states, and support a model in which developmental canalization is not a rigid irreversible path, but a highly plastic trajectory.

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SETD7 promotes lateral plate mesoderm formation by modulating the Wnt/b-catenin signaling pathway

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Selective activation of FZD2 and FZD7 reveals non-redundant function during mesoderm differentiation

Project description:Wnt-ßcatenin signalling controls stem cell self-renewal and cell fate decisions and therefore its precise control could influence differentiation protocols efficiency and cell therapy efforts. During gastrulation, Wnt-ßcatenin signalling dictates lineage bifurcation choices leading from pluripotency to distinct primitive streak patterning, ultimately resulting in various mesendoderm cell types. However, the nature of the Wnt receptors involved in this process and how their signaling dynamics impact mesoderm specification remain elusive. Here, we used selective Frizzled and LRP5/6 antibody-based agonists (FLAgs) to investigate the function and activation kinetics of Frizzled receptor complexes during directed mesoderm differentiation of hPSCs. We found that FZD2 and FZD7 are expressed at the surface of hPSCs and that their activation triggers ßcatenin signaling with different kinetics thereby influencing mesoderm patterning choices. Using bulk and single-cell RNA sequencing, we showed that FZD7 activation promotes lineage commitment towards both paraxial and lateral mesoderm whereas FZD2 engagement preferentially induces paraxial mesoderm. Mechanistically, our results demonstrate that although the short-term response following FZD2 and FZD7 activation is similar, ßcatenin signaling kinetics differs. FZD2 activation results in a sustained Wnt activation profile that drives hPSCs differentiation to paraxial mesoderm while blocking lateral mesoderm. In contrast, FZD7 activation kinetics consists of a similar initial activation followed by dampening of the response to a low level of ßcatenin signaling that is permissive for lateral mesoderm induction in addition to paraxial mesoderm specification. Our results suggest that the function of FZD2 and FZD7 during mesoderm specification is non-redundant and that their selective activation to temporally modulate Wnt-ßcatenin signaling can be leveraged for precise directed differentiation outcomes.

2025-03-05 | GSE267334 | GEO

Human Mesenchymal Stem / Stromal Cells (hMSCs) treated with Eltrombopag show increase of the hematopoietic supporting ability

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